RESUMO
Breast cancer is the most common type of cancer among women. The study of the mechanisms of metastasis, the main cause of death from breast cancer, as well as the search for new markers for early diagnosis and prognosis of breast cancer, is an extremely topical issue. New perspectives in the diagnosis and treatment of breast cancer are opened by the mechanisms of gene regulation involving non-coding RNAs, in particular, long non-coding RNAs (lncRNAs). In this work, we analyzed the methylation levels of seven lncRNA genes (MEG3, SEMA3B-AS1, HAND2-AS1, KCNK15-AS1, ZNF667-AS1, MAGI2-AS3, and PLUT) by quantitative methyl-specific PCR on a set of 79 paired (tumor/normal) samples of breast cancer. Hypermethylation of all seven lncRNA genes was revealed, and hypermethylation of HAND2-AS1, KCNK15-AS1, MAGI2-AS3, and PLUT was detected in breast cancer for the first time. It was found that the level of meth ylation of the studied lncRNA genes correlated statistically significantly with the stage of the tumor process, the size of the tumor, and the presence of metastases in the lymph nodes. Thus, methylation of the seven studied lncRNA genes is associated with the development and progression of breast cancer, and these genes can be useful as potential markers in the diagnosis and prognosis of breast cancer.
Assuntos
Neoplasias da Mama , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Adulto , IdosoRESUMO
There are three types of metastases in ovarian cancer: lymphogenous, hematogenous, and peritoneal. Dissemination of the tumor in the peritoneum is directly related with the development of ascites and a poor prognosis. The purpose of this study is to determine changes in the methylation level of a group of long non-coding RNA (lncRNA) genes at different stages of ovarian cancer progression. The methylation level of 7 lncRNA genes (LINC00472, LINC00886, MAFG-DT, SNHG1, SNHG6, TP53TG1, and TUG1) was studied by quantitative methyl-specific PCR in 93 samples of ovarian tumors and 75 paired samples of histologically normal tissue, as well as in 29 peritoneal macroscopic metastases. Using the nonparametric Mann-Whitney test, a significant (p<0.001) increase in the level of methylation of the LINC00886, SNHG1, SNHG6, and TUG1 genes in the tumor tissue was shown. For the LINC00472, LINC00886, and SNHG6 genes, a significant relationship was found with the clinical stage (p≤0.001), as well as with the appearance of metastases for the LINC00472 (p<0.001) and SNHG6 (p=0.005) genes. There was a significant increase in the level of methylation of MAFG-DT and TP53TG1 (p<0.001) genes, as well as a decrease in LINC00886 (p=0.003) in peritoneal metastases relative to the primary focus. Methylation of the LINC00472 and SNHG6 genes can be considered as a factor in initiating ovarian cancer metastasis, and methylation of the LINC00886, MAFG-DT, and TP53TG1 genes as a colonization factor for metastases in the peritoneum. Thus, a relationship between methylation of a group of lncRNA genes at different stages of ovarian cancer dissemination was shown, which is important for understanding the mechanisms of these processes and for developing innovative approaches to ovarian cancer therapy.
Assuntos
Neoplasias Ovarianas , RNA Longo não Codificante , Humanos , Feminino , Metilação de DNA/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Proliferação de Células/genéticaRESUMO
One of the etiological causes of dry eye disease (DED) is systemic autoimmune diseases (AID): primary Sjögren's syndrome (PSS), rheumatoid arthritis (RA); their manifestation may begin with ophthalmic symptoms. The relationship of PSS and RA with genetic factors is proven. The contribution of polymorphic markers of the genes THBS1, MUC1, TRIM21, STAT4, PTPN22 in the development of these diseases is established, as well as their connection with the development of DED. A panel of genetic markers for evaluating the risk of developing DED in PSS and RA is developed, and its sensitivity and specificity is determined. PURPOSE: The aim of the study was to determine the prognostic significance of a panel of polymorphic gene markers in the development of dry eye syndrome in patients with primary Sjögren's syndrome and rheumatoid arthritis over a five-year follow-up period. MATERIAL AND METHODS: Patients with a verified diagnosis of PSS and RA without signs of DED were examined (n=35 and n=42, respectively). The control group included 82 volunteers without AID and DED. The observation period was 5 years. Every year all study subjects underwent an ophthalmological clinical and functional examination. RESULTS: Dry eye disease had developed in groups of patients with AID with predisposing genotypes of polymorphic markers of the genes THBS1, MUC1, TRIM21, STAT4, PTPN22. The peak of DED development in these patients was in the third year of the follow-up. As a result of ROC analysis, it was found that the sensitivity and specificity of determining the predisposing genotypes of polymorphic markers of the THBS1, MUC1, TRIM21, STAT4, PTPN22 genes was 68 and 87%, respectively (p<0.0001). CONCLUSION: Genetic research methods are essential for minimally invasive early diagnosis of dry eye disease, and can subsequently become the basis for a personalized approach to its treatment.